Is CCT7 p.Thr519Ala (c.1555A>G) pathogenic?

CCT7 p.Thr519Ala (c.1555A>G) is classified Uncertain significance in CCT7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-30). AlphaMissense: likely pathogenic (0.9297); Absent from gnomAD v4.1.

How common is CCT7 p.Thr519Ala (c.1555A>G) in the general population?

CCT7 p.Thr519Ala (c.1555A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCT7 p.Thr519Ala (c.1555A>G)?

AlphaMissense predicts likely pathogenic (score 0.9297) — an in-silico prediction, not a clinical call.

CCT7 p.Thr519Ala

c.1555A>G · rs2529861359 · VCV2553082

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9297 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9297	likely pathogenic
REVEL	0.806	moderately pathogenic-leaning
SaProt	LLR -12.20	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.4	GERP 1.9, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 3,687 bp · p 0.00024 · regional, not allelic
Overall
CADD	24.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CCT7
Protein: p.Thr519Ala
Coding: c.1555A>G
MANE Select: NM_006429
dbSNP: rs2529861359
Type: single nucleotide variant
Location: chr2:73252784 (GRCh38)
Gene constraint: LOEUF 0.455 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 89.03 · 70 PDB
Residue 519: a β-strand

Full CCT7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCT7 p.Ala101Thr Uncertain significance ★ ⚠ same type
CCT7 p.Ala182Thr Uncertain significance ★ ⚠ same type
CCT7 p.Ala299Gly Uncertain significance ★ ⚠ same type
CCT7 p.Ala502Val Uncertain significance ★ ⚠ same type
CCT7 p.Ala506Val Uncertain significance ★ ⚠ same type
CCT7 p.Ala510Val Uncertain significance ★ ⚠ same type
CCT7 p.Arg126Cys Uncertain significance ★ ⚠ same type
CCT7 p.Arg344Gln Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/cct7-p-thr519ala (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown